Role of Fusion Gene Holds Promise of Therapy for Cancers, Including Prostate
May 23, 2012 -- Prostate Cancer Foundation funded research has shown that 50 percent of all prostate cancers carry the TMPRSS2-ERG gene fusion, an abnormal juxtaposition of TMPRSS2 and ERG genes. The product of this gene fusion is the protein ERG, which functions in the cancer cell as a protein that turns on “bad” genes and switches off the “good” genes. Despite this understanding, it has remained unclear what the precise mechanism by which ERG effects tumor growth and activity. Now, PCF-funded researchers at Weill Cornell Medical College, led by senior author Dr. Mark Rubin, have identified the process by which ERG facilitates alterations in global gene expressions in prostate cancer cells.
DNA is stored in the cell in a tightly packed complex, known as chromatin. Normal cell chromatin adopt a unique, non-random, three dimensional architecture that governs which DNA will be open or closed to allow gene expression. The study, published in the Proceedings of the National Academy of Sciences (PNAS), shows that in prostate cancer cells, the product of the abnormal fusion genes, ERG, changes this 3D topology of chromatin. These global changes in chromatin organization are translated into altered expression of cellular genes, resulting in switching “on” and “off” genes in a pro-cancer fashion.
In a statement to Science Daily, Dr. Rubin adds that if such an oncogenic protein (like ERG) has the power to throw the switch on thousands of genes, a novel treatment may be able to turn that switch off. “If we understand how this works, then we may be able to borrow that trick to target many genes simultaneously. This discovery would hold a lot of promise for cancer therapy,” shared Rubin.
This study has broad implications for other cancers as well, as genomic alterations frequently result in oncogenic transcription factor expression.
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